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1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

 Haneul Kim  ;  Seungye Baek  ;  Seung Min Hong  ;  Jaeseon Lee  ;  Seung Min Jung  ;  Jennifer Lee  ;  Mi La Cho  ;  Seung Ki Kwok  ;  Sung Hwan Park 
 JOURNAL OF KOREAN MEDICAL SCIENCE, Vol.35(6) : e40, 2020-02 
Journal Title
Issue Date
Antibodies, Monoclonal, Humanized* / therapeutic use ; Antirheumatic Agents* / therapeutic use ; Arthritis, Rheumatoid* / drug therapy ; Humans ; Leukocytes, Mononuclear ; Osteogenesis / drug effects ; Receptors, Interleukin-6 / immunology ; Retrospective Studies ; Vitamin D / analogs & derivatives* ; Vitamin D / blood ; Vitamin D / therapeutic use
Vitamin D ; Rheumatoid Arthritis ; Tocilizumab
Background: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab. Methods: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)(2)D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH) D levels (>= 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% +/- 15.5% vs. 52.7% +/- 20.7%, P= 0.004), and lower disease activity (91.2% vs. 70.3%, P= 0.018) or remission (82.4% vs. 57.8%, P= 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)(2)D treatment synergistically suppressed IL-17 production and osteoclastogenesis. Conclusion: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)(2)D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Jung, SeungMin(정승민) ORCID logo https://orcid.org/0000-0003-3465-2181
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